Adipose tissue derived signals for metabolic and immunologic reprogramming in MASLD (A05)

• Subject Area: Gastroenterology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 535081457

The contribution of fat-derived signals to the pathogenesis of MASLD remains incompletely understood, as the complex interplay between adipose tissue, the immune system, and liver homeostasis is difficult to examine in standard models of MASLD. By taking advantage of lipodystrophic mice and patients suffering from a complete loss of fat tissue and steatohepatitis, we will address how adipose tissue modulates MASLD by controlling metabolic injury and hepatic inflammation. Lipodystrophy will furthermore serve as a model system to investigate how lipotoxic stress contributes to somatic mutations in hepatic T cells and how genetic mosaicism shapes hepatic inflammation in MASLD. In-depth immune cell characterizations, metabolic analyses, and fat transplantation models will serve to decipher mechanisms driving MASLD, allowing to develop new concepts for the treatment of MASLD.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 412: Metabolic dysfunction-associated steatotic liver disease: Translating mechanisms to tailored therapeutic concepts
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professorin Dr. Britta Siegmund; Dr. Carl Weidinger